Balanced mechanical forces and microtubule contribution to fibroblast contraction

Abstract

Fibroblast locomotion is thought to generate tractional forces which lead to contraction and reorganisation of collagen in tissue development and repair. A culture force monitor device (CFM) was used to measure changes in force in fibroblast populated collagen lattices, which resulted from cytoskeletal reorganisation by cytochalasin B, colchicine, vinblastine, and taxol. Microfilament disruption abolished contraction forces, microtubule disruption elicited a new peak of contraction, while taxol stabilisation of microtubules produced a gradual fall in measured force across the collagen gel. Based on these measurements, it is suggested that the cell can be viewed as an engineering structure in which residual intracellular forces, from contractile microfilaments, exert compressive loading on microtubular elements. This microtubular structure appears to act as a “balanced space frame” (analogous to an aeroplane chassis), maintaining cell shape and consequently storing a residual internal tension (RIT). In dermal fibroblasts this hidden RIT was up to 33% of the measurable force exerted on the collagen gel. Phenotypic differences between space frame organisation and RIT levels could explain site and pathological variations in fibroblast contraction.